ABSTRACT Obsessive-compulsive disorder (OCD) is a chronic mental illness affecting 4-7 million people in the US. Patients are impaired in multiple Research Domain constructs. Medication and behavioral therapies yield inadequate symptom relief in 50-70% of patients. As a result, OCD remains a leading worldwide cause of disability, equivalent to more visible disorders such as schizophrenia. Roughly 1/3 of patients are unable to work due to their symptoms and their caregivers report profound, life-impairing stress. More recently, the field has focused on deep brain stimulation (DBS). However, about a third of the patients who undergo DBS receive no meaningful benefit. We propose a primarily retrospective investigation of imaging-based targeting for Deep Brain Stimulation (DBS) for severe obsessive-compulsive disorder (OCD). We aim to increase response rates while testing imaging biomarkers that could guide therapeutic intervention. Our hospital is the highest-volume site in the US using DBS at the ventral capsule/ventral striatum (VC/VS) for the treatment of intractable OCD. A major contributor to imperfect response is that DBS is implanted at standard coordinates across patients, without accounting for variation in VC/VS anatomy. Our investigation will study imaging markers that may target ventral capsule/ventral striatum (VC/VS) for DBS to patient-specific brain circuitry. We hypothesize that clinical response will be related to the degree that the DBS electrical field influences orbitofronto-thalamic fibers and the nucleus accumbens grey matter. If we are successful in identifying a biomarker during this three-year retrospective study, a future prospective clinical trial will target DBS implants to the newly identified structures in a patient-specific fashion.